Human melanoma cells secrete and respond to placenta growth factor and vascular endothelial growth factor

The vascular endothelial growth factor is produced by a large variety of hu man tumors, including melanoma, in which it appears to play an important ro le in the process of tumor-induced angiogenesis, Little information is avai lable on the role of placenta growth factor, a member of the vascular endot helial growth factor family of cytokines, in tumor angiogenesis, even thoug h placenta growth factor/vascular endothelial growth factor heterodimers ha ve been recently isolated from tumor cells. To investigate the role of plac enta growth factor and vascular endothelial growth factor homodimers and he terodimers in melanoma angiogenesis and growth, 19 human melanoma cell Line s derived from primary or metastatic tumors were characterized for the expr ession of these cytokines and their receptors, Release of placenta growth f actor and vascular endothelial growth factor polypeptides into the supernat ant of human melanoma cells was demonstrated. Reverse transcriptase polymer ase chain reaction analysis showed the presence of mRNAs encoding at least three different vascular endothelial growth factor isoforms (VEGF(121), VEG F(165), and VEGF(189)) and transcripts for two placenta growth factor isofo rms (PlGF-1 and PlGF-2) in human melanoma cells. In addition, placenta grow th factor expression in human melanoma in vivo was detected by immunohistoc hemical staining of tumor specimens. Both primary and metastatic melanoma c ells were found to express the mRNAs encoding for vascular endothelial grow th factor and placenta growth factor receptors (KDR, Flt-1, neuropilin-1, a nd neuropilin-2), and exposure of melanoma cells to these cytokines resulte d in a specific proliferative response, supporting the hypothesis of a role of these angiogenic factors in melanoma growth.